Prognostic value of sarcopenia in adults with solid tumours: A meta-analysis and systematic review

BackgroundBody composition plays an important role in predicting treatment outcomes in adults with cancer. Using existing computed tomographic (CT) cross-sectional imaging and readily available software, the assessment of skeletal muscle mass to evaluate sarcopenia has become simplified. We performed a systematic review and meta-analysis to quantify the prognostic value of skeletal muscle index (SMI) obtained from cross-sectional CT imaging on clinical outcomes in non-haematologic solid tumours.MethodsWe searched PubMed and the American Society Clinical Oncology online database of meeting abstracts up to October 2015 for relevant studies. We included studies assessing the prognostic impact of pre-treatment SMI on clinical outcomes in patients with non-haematologic solid tumours. The primary outcome was overall survival (OS) and the secondary outcomes included cancer-specific survival (CSS), disease-free survival (DFS), and progression-free survival (PFS). The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated.ResultsA total of 7843 patients from 38 studies were included. SMI lower than the cut-off was associated with poor OS (HR = 1.44, 95% CI = 1.32–1.56, p < 0.001). The effect of SMI on OS was observed among various tumour types and across disease stages. Worse CSS was also associated with low SMI (HR = 1.93, 95% CI = 1.38–2.70, p < 0.001) as well as DFS (HR = 1.16, 95% CI = 1.00–1.30, p = 0.014), but not PFS (HR = 1.54, 95% CI = 0.90–2.64, p = 0.117).ConclusionsThis meta-analysis demonstrates that low SMI at cancer diagnosis is associated with worse survival in patients with solid tumours. Further research into understanding and mitigating the negative effects of sarcopenia in adults with cancer is needed.     

Esophagectomy With Three-Field Versus Two-Field Lymphadenectomy for Middle and Lower Thoracic Esophageal Cancer: Long-Term Outcomes of a Randomized Clinical Trial

IntroductionThe optimal extent of lymphadenectomy during esophagectomy remains unclear. In this trial, we aim to clarify whether three-field (cervical-thoracic-abdominal) lymphadenectomy improved patient survival over two-field (thoracic-abdominal) lymphadenectomy for esophageal cancer.MethodsBetween March 2013 and November 2016, a total of 400 patients with middle and lower thoracic esophageal cancer were included and randomly assigned to undergo esophagectomy with either three- or two-field lymphadenectomy at a 1:1 ratio. Analyses were done according to the intention-to-treat principle. The primary end point was overall survival (OS), calculated from the date of randomization to the date of death from any cause.ResultsDemographic characteristics were similar in the two arms. The median follow-up time was 55 months (95% confidence interval [CI]: 52–58). OS (hazard ratio [HR] = 1.019, 95% CI: 0.727–1.428, p = 0.912) and the disease-free survival (DFS) (HR = 0.868, 95% CI: 0.636–1.184, p = 0.371) were comparable between the two arms. The cumulative 5-year OS was 63% in the three-field arm, as compared with 63% in the two-field arm; 5-year DFS was 59% and 53%, respectively. On the basis of whether the patients had mediastinal or abdominal lymph node metastasis or not, OS was also comparable between the two arms. In this cohort, only advanced tumor stage (pathologic TNM stages III–IV) was identified as the risk factor associated with reduced OS (HR = 3.330, 95% CI: 2.140–5.183, p < 0.001).ConclusionsFor patients with middle and lower thoracic esophageal cancer, there was no improvement in OS or DFS after esophagectomy with three-field lymphadenectomy over two-field lymphadenectomy.     

Treatment and outcome trends and predictors of overall survival of rectal melanoma: Analysis of the National Cancer Database

BackgroundWe aimed to assess characteristics, treatment, and outcomes of rectal melanoma (RM).MethodsThis retrospective cohort study looked at patients with RM from National Cancer Database (2004–2019) analyzed characteristics and outcomes of the entire cohort and across three time periods (2004–2009; 2010–2014; 2015–2019). Main outcome measures were change in treatment and survival trends across time periods and overall survival (OS).Results641 patients (58.5% female; mean age: 68.2 ± 13.6 years) were included. OS rate was 26%; median survival duration was 17.9 (IQR: 15.93–20.67) months. There was a significant decrease in the use of chemotherapy (17.3%–6.6%; p = 0.001) and surgery (62.9%–41.8%; p = 0.00004) but increased use of immunotherapy (11.9%–52%; p < 0.001) across time periods. OS was longer in the last time period than in the first two (21.8 vs 16.8 vs 16.5 months; p = 0.09). Surgical excision was an independent predictor of improved OS (HR = 0.266, 95%CI: 0.089–0.789, p = 0.017) whereas older age (HR = 1.039, 95%CI: 1.007–1.072, p = 0.016), positive resection margins (HR = 5.06, 95%CI: 1.902–13.48, p = 0.001) and metastasis (HR = 34.62, 95%CI: 3.973–301.6, p = 0.001) were predictors of poor survival.ConclusionsOver time, chemotherapy and surgery have been used less often in the treatment of RM while the use of immunotherapy increased by more than four-fold. Older age, surgical treatment, positive resection margins, and metastasis were predictive of survival of RM.     

Changes in Ki-67 in Residual Tumor and Outcome of Primary Inflammatory Breast Cancer Treated With Trimodality Therapy

BackgroundLimited data are available on the prognostic role of Ki-67 changes in residual tumors after neoadjuvant chemotherapy in primary inflammatory breast cancer (IBC) patients treated with trimodality therapy. This study aims to evaluate changes in Ki-67 associated with disease-free survival (DFS) and overall survival (OS) in IBC patients without pathological complete response.Patients and MethodsWe identified a cohort of primary IBC patients with matched pre- and posttreatment samples treated with anthracycline and taxane-based regimen. All patients had a pathological evaluation, including ER, PR, HER2 status, and Ki-67 expression performed both at diagnostic core biopsy and at final surgery. Kaplan–Meier and Cox proportional hazards methods were used to assess DFS and OS rates and their relationship with clinicopathological features.ResultsTwo hundred and ten patients with stage III IBC were included. Sixty-three percent of residual tumors showed a decrease in Ki-67 positivity by at least 1%. The decrease of Ki-67 significantly correlated with better DFS (p = .001) and OS (P = .010) compared with no decrease, particularly in the luminal B-like and HER2-positive subgroups. The multivariate analysis showed that the decrease in Ki-67 level had a significant positive predictive value on DFS (HR = 0.47, 95% CI: 0.33-0.67; P< .001) and OS (HR = 0.59, 95% CI: 0.36-0.82; P= .004) in all IBC patients.ConclusionThe decrease of Ki-67 expression after neoadjuvant chemotherapy has a prognostic significance in IBC patients with residual disease. Evaluation of Ki-67 changes may help to identify subgroups of patients with worse outcome to receive novel treatment in this setting.     

Allele Frequency–Adjusted Blood-Based Tumor Mutational Burden as a Predictor of Overall Survival for Patients With NSCLC Treated With PD-(L)1 Inhibitors

IntroductionBlood-based tumor mutational burden (bTMB) has been studied to identify patients with NSCLC who would benefit from anti-programmed cell death protein 1 (anti-PD-1) or anti-programmed death ligand 1 (anti-PD-L1) therapies. However, it failed to predict overall survival (OS) benefits, which warrants further exploration.MethodsThree independent cohorts of patients with NSCLC treated with immunotherapy were used in this study. A new bTMB algorithm was first developed in the two independent cohorts (POPLAR, N = 211, and OAK, N = 462) and further validated in the third National Cancer Center (NCC) cohort (N = 64).ResultsbTMB-H (bTMB ≥ cutoff point) was not associated with favorable OS after immunotherapy regardless of the cutoff points in either the POPLAR and OAK or the NCC cohorts (p > 0.05) owing to its correlation with the amount of circulating tumor DNA, which was associated with poor OS. In the POPLAR and OAK cohorts, with allele frequency (AF) adjustment, a high AF bTMB (HAF-bTMB, mutation counts with an AF > 5%) was strongly correlated with the amount of circulating tumor DNA (Pearson r = 0.65), whereas a low AF bTMB (LAF-bTMB, mutation counts with an AF ≤ 5%) was not (Pearson r = 0.09). LAF-bTMB-H was associated with favorable OS (hazard ratio [HR] = 0.70, 95% confidence interval [CI]: 0.52–0.95, p = 0.02), progression-free survival (PFS; HR = 0.62, 95% CI: 0.47–0.80, p < 0.001), and objective response rate (ORR) (p < 0.001) after immunotherapy but not chemotherapy, with a cutoff point of 12 trained in the POPLAR cohort and validated in the OAK cohort. The LAF-bTMB algorithm was further validated in the NCC cohort in which LAF-bTMB-H was associated with OS (HR = 0.20, 95% CI: 0.05–0.84, p = 0.02), PFS (HR = 0.30, 95% CI: 0.13–0.70, p = 0.003), and ORR (p = 0.001).ConclusionsWe developed and validated a new LAF-bTMB algorithm as a feasible predictor of OS, PFS, and ORR after anti-PD-(L)1 therapies in patients with NSCLC, which needs to be prospectively validated.     

Electronic FRAIL score may predict treatment outcomes in older adults with myeloma

IntroductionFrailty is a known risk factor for older patients with myeloma. Here we present realworld data using a computer-generated frailty assessment score (FRAIL score), based on 5 clinically derived parameters, in predicting patient outcomes.MethodsOlder patients with newly diagnosed multiple myeloma who received frontline treatment with cyclophosphamide-bortezomib-dexamethasone had their FRAIL score retrospectively assessed. Treatment outcomes were assessed using standard IMWG criteria, and event free survival and overall survival determined.Results155 patients were analysed. Compared to those who were assessed as non-frail (FRAIL score 0–1) likely-frail patients (score ≥ 2) were less likely to complete the full course of treatment (24.3% vs 53.4%, p = 0.002), and more likely to terminate treatment due to toxicities (35.1% vs 22.0%, p = 0.109), as well as having a greater number of patients stop treatment early for reasons other than toxicity or progression (27.0% vs 10.2%, p = 0.010). After a median follow up of 42.5 months, likely-frail patients were found to have a trend for shorter event-free survival (median EFS, 8.7 vs 17.9 months, p = 0.064) and statistically inferior overall survival (median OS, 30.2 vs 49.8 months, p < 0.001). After adjusting for age, stage, and Charlson comorbidity index, FRAIL score was prognostic for OS (HR = 3.47, 95% CI 1.88–6.4), but not EFS (HR = 1.28, 95%CI 0.79–2.06).ConclusionThe FRAIL score is independently predictive of overall survival in older patients with myeloma receiving bortezomib-based induction chemotherapy and can help identify those patients more likely to experience treatment toxicity.     

Postoperative Radiotherapy for Completely Resected Masaoka/Masaoka-Koga Stage II/III Thymoma Improves Overall Survival: An Updated Meta-Analysis of 4746 Patients

IntroductionOur systematic review and meta-analysis aimed to evaluate the effect of postoperative radiotherapy (PORT) on completely resected Masaoka/Masaoka-Koga (M/MK) stage II/III thymomas.MethodsWe systematically searched four online databases and included studies that compared surgery alone versus surgery plus a PORT for completely resected M/MK stage II/III thymoma. The multivariate-adjusted hazard ratios (HRs) of overall survival (OS) and disease-free survival were evaluated as the primary and secondary end points, respectively. We performed a subgroup analysis for OS with respect to M/MK stage II, III, and inseparable II/III cases. A generic inverse variance meta-analysis using a random model was conducted.ResultsFive studies including 4746 patients (among them, 2408 patients received PORT) met our selection criteria. A meta-analysis of these five studies revealed that PORT was associated with a significantly better OS (HR = 0.68, 95% confidence interval [CI]: 0.57–0.83, p < 0.001, I² = 0%, p for heterogeneity = 0.97). Subgroup analyses for M/MK stage II disease (HR = 0.63, 95% CI: 0.44–0.91, p = 0.01, I² = 0%, p for heterogeneity = 0.80) and M/MK stage III disease (HR = 0.72, 95% CI: 0.55–0.95, p = 0.02, I² = 0%, p for heterogeneity = 0.84) revealed similar results. PORT was not associated with an improved disease-free survival (HR = 0.96, 95% CI: 0.70–1.33, p = 0.83, I² = 0%, p for heterogeneity = 0.72).ConclusionsCurrently available evidence from observational studies suggests PORT for patients with completely resected M/MK stage II/III thymoma. A randomized trial is warranted.     

Checkpoint Inhibitors in Metastatic EGFR-Mutated Non–Small Cell Lung Cancer—A Meta-Analysis

IntroductionWe performed a meta-analysis to assess the role of immune checkpoint inhibitors as second-line therapy in EGFR-mutant advanced NSCLC.MethodsRandomized trials comparing immune checkpoint inhibitors against chemotherapy were identified. We retrieved the hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) of the intention-to-treat population and EGFR mutation–defined subgroups. We used the fixed-effects inverse variance–weighted method to pool estimates of treatment efficacy. Statistical tests were two sided.ResultsIn the three included studies that compared immune checkpoint inhibitors (nivolumab [n = 292], pembrolizumab [n = 691], and atezolizumab [n =144]) against docetaxel (n = 776), immune checkpoint inhibitors significantly prolonged OS over that with docetaxel overall (n = 1903, HR = 0.68, 95% CI: 0.61–0.77, p < 0.0001) and in the EGFR wild-type subgroup (n = 1362, HR = 0.66, 95% CI: 0.58–0.76, p < 0.0001) but not in the EGFR-mutant subgroup (n = 186, HR = 1.05, 95% CI: 0.70–1.55, p < 0.81; treatment-mutation interaction p = 0.03).ConclusionIn EGFR-mutant advanced NSCLC, immune checkpoint inhibitors do not improve OS over that with docetaxel. Mechanisms of acquired resistance to first-line tyrosine kinase inhibitor therapy should be elucidated to guide selection of second-line treatment for these patients.     

Patterns of Care and Treatment Outcomes of Elderly Patients with Stage I Esophageal Cancer: Analysis of the National Cancer Data Base

IntroductionThis study analyzes practice patterns, treatment-related mortality, survival, and predictors thereof in elderly patients with early-stage esophageal cancer (EC).MethodsThe National Cancer Data Base was queried for cT1-2 N0 EC in patients 80 years of age and older. Patients were divided into four treatment groups: observation (Obs), chemoradiotherapy (CRT), local excision (LE), and esophagectomy (Eso). Patient, tumor, and treatment parameters were extracted and compared. Analyses were performed on overall survival (OS) and postoperative 30- and 90-day mortality.ResultsA total of 923 patients from 2004 to 2012 were analyzed. Of these, 43% underwent clinical Obs, 22% underwent CRT, 25% underwent LE, and 10% underwent Eso. Patients undergoing Obs were older, had more comorbidities, were treated at nonacademic centers, and lived 25 miles or less from the facility. Patients receiving an operation (Eso or LE) were more often younger, male, white, and in the top income quartile. The postoperative 30-day mortality rates in the LE and Eso groups were 1.3% and 9.6%, respectively (p < 0.001) and increased to 2.6% and 20.2% at 90 days, respectively (p < 0.001). The 5-year OS rate was 7% for Obs, 20% for CRT, 33% for LE, and 45% for Eso (p < 0.001). Multivariate analyses showed improved OS with any local definitive therapy: CRT (hazard ratio [HR] = 0.42, 95% confidence interval [CI]: 0.34–0.52, p < 0.001), LE (HR = 0.3, 95% CI: 0.24–0.38, p < 0.001), and Eso (HR = 0.32, 95% CI: 0.23–0.44, p < 0.001).ConclusionsThere are noteworthy demographic, socioeconomic, and regional disparities influencing management of elderly patients with stage I EC. Despite high rates of Obs, careful consideration of all local therapy options is warranted, given the improved outcomes with treatment.     

A systematic review and meta-analysis on the impact of pre-operative neutrophil lymphocyte ratio on long term outcomes after curative intent resection of solid tumours

IntroductionThere is increasing evidence to suggest that cancer-associated inflammation is associated with poorer long-term outcomes. Various markers have been studied over the past decade in an attempt to improve selection of patients for surgery. This meta-analysis explored the association between the neutrophil-lymphocyte ratio and prognosis following curative-intent surgery for solid tumours.MethodsStudies were identified from US National Library of Medicine (Medline) and the Exerpta Medica database (EBASE) performed in March 2013. A systematic review and meta-analysis were performed to generate combined hazard ratios for overall survival (OS) and disease-free survival (DFS).ResultsForty-nine studies containing 14282 patients were included. Elevated NLR was associated with poorer overall survival [HR: 1.92, 95% CI (1.64–2.24)] (p < 0.001) and disease-free survival [HR: 1.99, 95% CI (1.80–2.20)] (p < 0.001). Significant heterogeneity was found with an I² of 77% and 97% for OS and DFS respectively. Subgroup analyses demonstrated that gastro-intestinal malignancies; mainly gastric [HR: 1.97, 95% CI (1.41–2.76)], colorectal [HR: 1.65, 95% CI (1.21–2.26)] and oesophageal [HR: 1.48, 95% CI (0.91–2.42)] cancers were predictive of OS (I² = 54.3%). A separate analysis for studies using an NLR cutoff of 5 demonstrated significantly poorer outcomes [HR: 2.18, 95% CI (1.74–2.73)] (p = 0.002) with less heterogeneity (I² = 58%).ConclusionElevated NLR correlates with poorer prognosis. It potentially represents a simple, robust and reliable measure that may be useful in identifying high-risk groups who could benefit from adjuvant therapy.     

Comparative study on the oncological prognosis of laparoscopy and laparotomy for stage IIA1 cervical squamous cell carcinoma

ObjectiveTo compare the 5-year overall survival (OS) and disease-free survival (DFS) rate of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for stage IIA1 cervical squamous cell carcinoma.MethodsBased on a large database containing information on the clinical diagnosis and treatment of cervical cancer in China, the oncological outcomes of the two surgical approaches for stage IIA1 cervical squamous cell carcinoma were compared after 1:2 propensity score matching (PSM).ResultsAfter 1:2 propensity score matching (PSM), 510 patients were included in the LRH group, and 999 patients were included in the ARH group. LRH showed a similar 5-year OS but a lower DFS rate (81.3% vs. 87.4%, P = 0.018) than ARH. In the multivariate analysis, LRH was identified as an independent risk factor for worse 5-year DFS (HR = 1.569, 95% CI: 1.131–2.176, P = 0.007). Among patients with a tumour size <2 cm, the LRH and ARH groups showed similar OS and DFS rates after 1:2 PSM, and multivariate analysis showed that the surgical approach was not an independent risk factor affecting the OS or DFS rate. Among patients with a tumour size ≥2 cm and <4 cm, there was no difference in OS between the LRH and ARH groups after matching, but the DFS in the LRH group was significantly lower than that in the ARH group (81.1% vs 86.2%, P = 0.034). In the multivariate analysis, the laparoscopic approach was not associated with OS but was independently associated with worse DFS (HR = 1.546, 95% CI: 1.094–2.185, P = 0.014).ConclusionsLRH was associated with poorer 5-year DFS than ARH in patients with stage IIA1 cervical squamous cell carcinoma. However, LRH showed 5-year OS and DFS rates similar to those of ARH among patients with a tumour size <2 cm. For patients with a tumour size ≥2 cm and <4 cm, LRH showed a lower DFS rate than ARH.     

Improved Survival of Stage I Non–Small Cell Lung Cancer: A VA Central Cancer Registry Analysis

IntroductionThe combined impact of advances in diagnosis and treatment of stage I NSCLC has not been assessed comprehensively. To define the survival impact of modern staging and treatment techniques for clinical stage I NSCLC, the Veterans Administration Central Cancer Registry, a database of U.S. veterans in whom the disease was diagnosed in the Veteran’s Health Administration, was queried. From this database, patients who had stage I NSCLC diagnosed from 2001 to 2010 and were treated with either surgery or radiation were identified.MethodsOverall survival (OS) and lung cancer–specific survival were determined. Propensity score matching and Cox multivariate analysis were used to adjust for baseline patient characteristics.ResultsA total of 11,997 patients were identified. The 4-year OS rate increased from 38.9% to 53.2% from 2001 to 2010 for all patients. Positron emission tomography and endobronchial ultrasound did not improve OS. Survival of radiated patients improved from 12.7% to 28.5%. The introduction of stereotactic body radiation therapy (SBRT) significantly improved OS (hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.54–0.68) and lung cancer–specific survival (HR = 0.39, 95% CI: 0.32–0.46) compared with conventionally fractionated radiation. The 4-year OS rate also improved after surgery (from 51.5% to 66.5%). This increase was associated with use of adjuvant chemotherapy, increased use of video-assisted thoracoscopic surgical procedures, and decreased pneumonectomy rates, with similar survival between open and video-assisted thoracoscopic surgical procedures. OS after lobectomy was superior to that after sublobar resection (HR = 0.82, 95% CI: 0.75–0.89). In the era of available SBRT (2008–2010), 4-year OS was not significantly different after sublobar resection or lobectomy for medically unfit patients (Charlson comorbidity index = 2) (55.4% and 58.1%, respectively; p = 0.69) but was significantly worse for fit patients (Charlson comorbidity index = 0–1) undergoing sublobar resection (55.5% and 68.0%, respectively; p < 0.001).OS (HR = 0.36, 95% CI: 0.35–0.38) and lung cancer–specific survival (HR = 0.31, 95% CI: 0.29–0.33) were improved after surgery as compared with after radiation, with the improvement maintained on matched comparison of lobectomy and SBRT.ConclusionsOS increased in veterans with a diagnosis of stage I NSCLC from 2001 to 2010; the increase was coincident with improved radiation and surgical techniques.     

Effectiveness of neoadjuvant chemotherapy on the survival outcomes of patients with resectable non-small-cell lung cancer: A meta-analysis of randomized controlled trials

PurposeTo determine the effectiveness of neoadjuvant chemotherapy (NACT) versus primary surgery on survival outcomes for resectable non-small-cell lung cancer (NSCLC) using an approach based on a meta-analysis.MethodsThe PubMed, EmBase, Cochrane library, and CNKI databases were systematically browsed to identify randomized controlled trials (RCTs) which met a set of predetermined inclusion criteria throughout January 2020. Hazard ratios (HRs) were applied for the pooled overall survival (OS) and progression-free survival (PFS) values, and the pooled survival rates at 1-year and 3-year were used as the relative risk (RR). All the pooled effect estimates with 95% confidence intervals (CIs) were calculated using the random-effects model.ResultsNineteen RCTs contained a total of 4372 NSCLC at I-III stages was selected for final meta-analysis. We noted NACT was significantly associated with an improvement in OS (HR: 0.87; 95%CI: 0.81–0.94; P < 0.001) and PFS (HR: 0.86; 95%CI: 0.78–0.96; P = 0.005). Moreover, the survival rate at 1-year (RR: 1.07; 95%CI: 1.02–1.12; P = 0.007) and 3-year (RR: 1.16; 95%CI: 1.06–1.27; P = 0.001) in the NACT group was significantly higher than the survival rate for the primary surgery group. Finally, the treatment effects of NACT versus primary surgery on survival outcomes might be different when stratified by the mean age of patients and the tumor stages.ConclusionsNACT could improve survival outcomes for patients with resectable NSCLC, suggesting its suitable future applicability for clinical practice. However, large-scale RCT should be conducted to assess the chemotherapy regimen on the prognosis of resectable NSCLC.     

The Impact of Postoperative Radiotherapy for Thymoma and Thymic Carcinoma

IntroductionThe optimal role for postoperative radiotherapy (PORT) for thymoma and thymic carcinoma remains controversial. We used the National Cancer Data Base to investigate the impact of PORT on overall survival (OS).MethodsPatients who underwent an operation for thymoma or thymic carcinoma were categorized into Masaoka-Koga stage groups I to IIA, IIB, III, and IV. Patients who did not undergo an operation or those who received preoperative radiation were excluded. Kaplan-Meier estimates of OS and univariate and multivariate Cox proportional hazards regression analyses were performed. Propensity score–matched analyses were performed to further control for baseline confounders.ResultsFrom 2004 to 2012, 4056 patients were eligible for inclusion, 2001 of whom (49%) received PORT. On multivariate analysis of OS in the thymoma cohort adjusted for age, WHO histologic subtype, Masaoka-Koga stage group, surgical margins, and chemotherapy administration, PORT was associated with superior OS (hazard ratio [HR] = 0.72, p = 0.001). Propensity score–matched analyses confirmed the survival advantage associated with PORT. Subset analysis indicated longer OS in association with PORT for patients with stage IIB thymoma (HR = 0.61, p = 0.035), stage III (HR = 0.69, p = 0.020), and positive margins (HR = 0.53, p < 0.001). The impact of PORT for stage I to IIA disease did not reach significance (HR = 0.76, p = 0.156).ConclusionsIn this large database analysis of PORT for thymic tumors, PORT was associated with longer OS, with the greatest relative benefits observed for stage IIB to III disease and positive margins. In the absence of randomized studies assessing the value of PORT, these data may inform clinical practice.     

Synergistic effect of clinicopathological factors on mortality risk in patients with differentiated thyroid cancer: An analysis using the SEER database

ObjectivesIn this study, we analyzed the effects of histology subtypes, lymph node N-stages, and the presence of extrathyroidal extensions on cancer-specific survival (CSS) and overall survival (OS) in patients with differentiated thyroid cancer.Materials and methodsCox proportional hazards regression analyses were carried out to evaluate the correlations between clinicopathological factors and CSS/OS. The combined effects of these factors on CSS and OS were then analyzed to determine the relative excess risk, attributable proportion, and synergy index. Kaplan-Meier curves were used to evaluate the mortality rate.ResultsA total of 86033 cases were included in the analysis. Histology subtype, N-stage, and extrathyroidal extension were all found to be risk factors for CSS (hazard ratio [HR] = 1.8, 95% confidence intervals [CI]: 1.4–2.3, p < 0.001; HR = 1.9, 95% CI: 1.6–2.3, p < 0.001; HR = 1.4, 95% CI: 1.0–1.9, p = 0.035, respectively). The risk factors for OS were histology subtype and N-stage (HR = 1.3, 95% CI; 1.2–1.5, p < 0.001; HR = 1. 4, 95% CI: 1.3–1.5, p < 0.001, respectively) but not extrathyroidal extension (HR = 1.1, 95% CI: 0.9–1.3, p = 0.228). Furthermore, histology subtype and N-stage, histology subtype and extrathyroidal extension, and N stage and extrathyroidal extension (relative excess risk, attributable proportion, and synergy index: 48.8, 0.9, 7.6; 50.2, 0.7, 3.9; 7.0, 0.3, 1.6; respectively) were found to have significant synergistic effects.ConclusionPatients with follicular thyroid carcinoma (FTC) and extrathyroidal extension or lymph node metastasis are at a higher risk of mortality. Histology subtype, N-stage, and extrathyroidal extension appear to have synergistic effects on the increased risk of poor CSS in patients. This result can in the further development of treatment guidelines to improve the outcome of FTC patients.     

Cemiplimab Plus Chemotherapy Versus Chemotherapy Alone in Advanced NSCLC: 2-Year Follow-Up From the Phase 3 EMPOWER-Lung 3 Part 2 Trial

IntroductionEMPOWER-Lung 3 part 2 (NCT03409614), a double-blind, placebo-controlled phase 3 study, investigated cemiplimab (antiprogrammed cell death protein 1) plus chemotherapy versus placebo plus chemotherapy in patients with advanced NSCLC without EGFR, ALK, or ROS1 aberrations, with either squamous or nonsquamous histology, irrespective of programmed death-ligand 1 levels. At primary analysis, after 16.4 months of follow-up, cemiplimab plus chemotherapy improved median overall survival (OS) versus chemotherapy alone (21.9 versus 13.0 mo, hazard ratio [HR] = 0.71, 95% confidence interval [CI]: 0.53–0.93, p = 0.014). Here, we report protocol-specified final OS and 2-year follow-up results.MethodsPatients (N = 466) were randomized 2:1 to receive histology-specific platinum-doublet chemotherapy, with 350 mg cemiplimab (n = 312) or placebo (n = 154) every 3 weeks for up to 108 weeks. Primary end point was OS; secondary end points included progression-free survival and objective response rates.ResultsAfter 28.4 months of median follow-up, median OS was 21.1 months (95% CI: 15.9–23.5) for cemiplimab plus chemotherapy versus 12.9 months (95% CI: 10.6–15.7) for chemotherapy alone (HR = 0.65, 95% CI: 0.51–0.82, p = 0.0003); median progression-free survival was 8.2 months (95% CI: 6.4–9.0) versus 5.5 months (95% CI: 4.3–6.2) (HR = 0.55, 95% CI: 0.44–0.68, p < 0.0001), and objective response rates were 43.6% versus 22.1%, respectively. Safety was generally consistent with previously reported data. Incidence of treatment-emergent adverse events of grade 3 or higher was 48.7% with cemiplimab plus chemotherapy and 32.7% with chemotherapy alone.ConclusionsAt protocol-specified final OS analysis with 28.4 months of follow-up, the EMPOWER-Lung 3 study continued to reveal benefit of cemiplimab plus chemotherapy versus chemotherapy alone in patients with advanced squamous or nonsquamous NSCLC, across programmed death-ligand 1 levels.     

The Impact of Postoperative Conformal Radiotherapy after Radical Surgery on Survival and Recurrence in Pathologic T3N0M0 Esophageal Carcinoma: A Propensity Score-Matched Analysis

IntroductionThe role of conformal radiotherapy (cRT) in thoracic esophageal squamous cell carcinoma (TESCC) has not been addressed in adjuvant settings. The aim of this study was to investigate whether postoperative radiotherapy using cRT after an R0 resection improves outcomes in pT3N0M0 TESCC compared with resection alone.MethodsThis study included 678 patients with pT3N0M0 TESCC who were treated at the Cancer Hospital, Chinese Academy of Medical Sciences, from January 2004 to December 2011. The patients were divided into two groups: a surgery plus cRT group (S+cRT group) comprising patients who underwent cRT after an R0 resection and a surgery group (S group), comprising a control group of patients who underwent an R0 resection alone. Propensity score matching was used to create patient groups that were balanced across several covariates (n = 83 in each group). Outcome measures included overall survival (OS), disease-free survival (DFS), and recurrence.ResultsIn the overall study cohort, 5-year OS (75.2% versus 58.5%, p = 0.004) and DFS (71.8% versus 49.2%, p = 0.001) rates were significantly higher in the S+cRT group than in the S group. These data were confirmed in the matched samples (5-year OS, 75.7% versus 58.8% [p = 0.017]; DFS, 71.7% versus 50.3% [p = 0.009]). The overall (p = 0.001) and locoregional (p = 0.004) recurrence rates in the S+cRT group were significantly lower than in the S group. Multivariate Cox analyses in the matched samples revealed that surgery and postoperative cRT were independently associated with longer OS (hazard ratio = 0.505, 95% confidence interval: 0.291–0.876, p = 0.015) and longer DFS (hazard ratio = 0.513, 95% confidence interval: 0.309–0.854, p = 0.010) than resection alone.ConclusionsPostoperative radiotherapy using cRT is strongly associated with improved OS and DFS in patients with pT3N0M0 TESCC. A multicenter, randomized phase III clinical trial is warranted to confirm these findings.     

Survival outcome and perioperative complication related to neoadjuvant chemotherapy with carboplatin and paclitaxel for advanced ovarian cancer: A systematic review and meta-analysis

ObjectiveTo compare the effectiveness and safety of neoadjuvant chemotherapy with carboplatin/paclitaxel followed by interval debulking surgery (NACT-IDS) to primary debulking surgery plus postoperative chemotherapy (PDS) for advanced ovarian cancer.MethodsA comprehensive systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Ovarian Cancer Committee. Multiple public search engines including PubMed/MEDLINE and the Cochrane Database, were searched in March 2019 using the entry keywords “ovarian cancer [all fields]" AND “interval debulking surgery [all fields]”, AND “neoadjuvant chemotherapy [all fields]”. Key inclusion criteria were prospective clinical trials examining platinum-based NACT for stage II-IV epithelial ovarian cancer. The primary outcome of interest was survival, and the secondary outcome was adverse events with each intervention.ResultsAfter screening 333 studies, four phase III randomized clinical trials were identified that met the inclusion criteria. These trials included 1692 women (847 receiving NACT-IDS and 845 receiving PDS). It was found that NACT-IDS and PDS had similar overall survival (hazard ratio [HR]: 0.97, 95% confidence interval [CI]: 0.87–1.07, P = 0.53) and progression-free survival (HR: 0.98, 95%CI: 0.90–1.08, P = 0.74). In contrast, NACT-IDS was associated with significantly lower rates of perioperative complications (odds ratio [OR] 0.27, 95%CI: 0.20–0.36, P < 0.001) and perioperative mortality (OR: 0.17, 95%CI: 0.06–0.50, P < 0.001) compared to PDS.ConclusionThis systematic review and meta-analysis suggests that NACT-IDS with carboplatin and paclitaxel does not negatively impact the survival of women with advanced ovarian cancer compared to PDS, while perioperative complications and mortality are significantly reduced by 70–80%.     

Prognostic relevance of disseminated tumour cells from the bone marrow of early stage breast cancer patients – Results from a large single-centre analysis

BackgroundThis is the largest single-centre study to determine the prognostic relevance of disseminated tumour cells (DTCs) from the bone marrow (BM) of stage I-III breast cancer patients. Additionally, we aimed to analyse the impact of DTC detection on adjuvant bisphosphonate (BP) treatment efficacy.MethodsBM aspirates were collected during primary surgery for early breast cancer (EBC; T1–4, N0–2, M0) at Tuebingen University, Germany, between January 2001 and January 2013. DTCs were identified by immunocytochemistry (pancytokeratin antibody A45/B-B3) and cytomorphology. We retrospectively estimated the influence of DTC detection and BP treatment on disease-free survival (DFS) and overall survival (OS) using univariate (log-rank test) and multivariate (cox regression) analysis.FindingsBM aspirates were available from 3141 patients. In 803 (26%) of these, DTCs were detectable. As compared to DTC-negative patients, DTC-positive patients more frequently had larger tumors (p < 0.001), lymph node involvement (p < 0.001), hormonal receptor positive tumours (p < 0.001) and HER2-positive tumours (p = 0.048). DTC-positive patients were at an increased risk of relapse (hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.34–2.25, p < 0.001) and death (HR 1.44 95% CI 1.13–1.86, p = 0.004). In the multivariate analysis DTCs were an independent predictor of DSF and OS. Additionally, BP treatment had no significant influence on DFS or OS in DTC-negative patients, while it was significantly associated with increased DFS (p < 0.001) and OS (p = 0.006) in DTC-positive patients.InterpretationThese data confirm the clinical validity of DTCs from the BM for prognostication of early breast cancer patients. Further studies are warranted to determine whether DTCs are predictive for adjuvant treatment efficacy using bisphosphonates.